title: Interleukin-22 mediates early host defense against Rhizomucor pusilluscan pathogens.
abstract: BACKGROUND
  In recent years, the fungal infectious disease zygomycosis has increased in incidence worldwide, especially among the immunodeficient population. Despite the rates of zygomycosis-related death and deformation being very high, the mechanism(s) by which the fungal pathogens cause these severe manifestations remain unknown.
  
  
  METHODS
  Using the associated Rhizomucor variabilis species, which can selectively induce cutaneous zygomycosis in otherwise healthy individuals, we investigated the host mechanisms of infection-related responses, including cytokine and chemokine expression as well as contributions of particular T cell subsets. siRNA specifically targeting IL-22,IL-17 and IFN-γ were used to down-regulate expression of those molecules.
  
  
  RESULTS
  In mouse models of infection, IL-22 was implicated in development of Rhizomucor spp.-induced skin lesions. In cultured human peripheral blood monocytes, R. pusilluscan, which is often found in immunodeficient patients, induced the production of IL-22, while R. variabilis did not. Moreover, Rhizomucor spp.-induced secretion of Il-22 from CCR6(+)CCR4(+)CCR10(+) cells was down-regulated by knockdown of IL-22 related signaling receptors, RORC and ARH.
  
  
  CONCLUSIONS
  Our data strongly suggest that avoidance of IL-22 may be one mechanism by which mucor species produce morbidity and mortality in infected individuals.
authors.affiliation: Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Hai-jing
authors.initials: HJ
authors.lastname: Fu
authors.forename: Yong-nian
authors.initials: YN
authors.lastname: Shen
authors.forename: Gui-xia
authors.initials: GX
authors.lastname: Lu
authors.forename: Huan
authors.initials: H
authors.lastname: Mei
authors.forename: Xin-zhi
authors.initials: XZ
authors.lastname: Cao
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Wei-da
authors.initials: WD
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009091:Mucormycosis / Q000276:immunology* / Q000382:microbiology; D034741:RNA, Small Interfering / Q000235:genetics; D020103:Rhizomucor / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D017931:DNA Primers; D007378:Interleukins; D034741:RNA, Small Interfering; D000097043:Interleukin-22